Homocysteine lowering and glutathione increasing effects of N-acetylcysteine in acute coronary syndrome

Several studies have suggested that increased homocysteine (Hcy) is a risk factor for cardiovascular (CVD) and atherothrombotic diseases because it affect both the vascular wall structure and the blood coagulation system. However, large randomised clinical trials have shown that, even though B-vitamin and folic acid supplementation reduced Hcy levels, there was no significant effect on CVD risk. Oxidative stress is another contributory factor to the etiology of many CVD and we have previously reported low concentrations of reduced glutathione (GSH) in CVD. GSH is an endogenous tripeptide with antioxidant properties and the ratio between reduced and oxidized (GSSG) forms is a major mechanism by which cells maintain redox balance. N-acetylcysteine (NAC), a drug used to prevent contrast-nephropathy after angiography, is a GSH synthesis precursor. Recent studies have also evidenced a Hcy-lowering activity of NAC in healthy subjects and in renal insufficiency bearing patients. In the present study we investigated the effect of NAC on Hcy and GSH levels in acute coronary syndrome (ACS) patients. Plasmatic Hcy and whole blood GSH and GSSG were measured in patients with ACS (n=20) before and 2, 6 and 24 hrs after an intravenous bolus (600 mg) of NAC. Mean Hcy concentrations significantly decreased up to 6 hours after bolus (-40.1 %, p<.0001), returning to basal levels at 24 hrs, while the profile of NAC concentrations showed an opposite behaviour. Whole blood GSH significantly increased after 24 hrs (+18.4 %, p=0.015) with a concomitant GSSG decrease (-23.8 %, p=0.03). These preliminary results suggest a beneficial effect of NAC administration in ACS patients. In conclusion, NAC may represent a therapeutic tool able to counteract both the oxidative stress status, by increasing GSH levels, and hyperhomocysteinemia condition, by reducing Hcy plasmatic levels.